Meng Yuan, Du Juan, Liu Ning, Qiang Yuanyuan, Xiao Lifei, Lan Xiaobing, Ma Lin, Yang Jiamei, Yu Jianqiang, Lu Guangyuan
Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, PR China.
Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan, PR China.
J Drug Target. 2023 Feb;31(2):142-151. doi: 10.1080/1061186X.2022.2125978. Epub 2022 Sep 20.
Depression is a serious mental illness and a prevalent condition with multiple aetiologies. The impact of the current therapeutic strategies is limited and the pathogenesis of the illness is not well understood. According to previous studies, depression onset is influenced by a variety of environmental and genetic factors, including chronic stress, aberrant changes in gene expression, and hereditary predisposition. Transcriptional regulation in eukaryotes is closely related to chromosome packing and is controlled by histone post-translational modifications. The development of new antidepressants may proceed along a new path with medications that target epigenetics. Histone deacetylase inhibitors (HDACis) are a class of compounds that interfere with the function of histone deacetylases (HDACs). This review explores the relationship between HDACs and depression and focuses on the current knowledge on their regulatory mechanism in depression and the potential therapeutic use of HDACis with antidepressant efficacy in preclinical research. Future research on inhibitors is also proposed and discussed.
抑郁症是一种严重的精神疾病，病因多样且普遍存在。当前治疗策略的效果有限，该疾病的发病机制尚未完全明确。根据以往研究，抑郁症的发作受多种环境和遗传因素影响，包括慢性应激、基因表达异常变化以及遗传易感性。真核生物中的转录调控与染色体包装密切相关，并受组蛋白翻译后修饰的控制。新型抗抑郁药的研发可能会沿着靶向表观遗传学的药物这条新途径进行。组蛋白去乙酰化酶抑制剂（HDACis）是一类干扰组蛋白去乙酰化酶（HDACs）功能的化合物。本综述探讨了HDACs与抑郁症之间的关系，重点关注目前关于它们在抑郁症中的调控机制以及HDACis在临床前研究中具有抗抑郁疗效的潜在治疗用途的知识。还提出并讨论了关于抑制剂的未来研究。
